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Luteal Phase Defect

As the cycle progresses there are changes that we can see in the endometrium. To see these changes, an office biopsy must be performed and the tissue needs to be examined under the microscope. This is the “endometrial biopsy”. Through the follicular phase, the only change is that the tissue gets a bit thicker, so we don’t biopsy here, we wait till after ovulation (the luteal phase). In the luteal phase the changes are very real. From day to day (or every couple of days) we can see changes in the cells. On day 16 the cells of the endometrium look different than they will on day 19, 22, 24 etc. In references books there are pictures of what the cells should look like on certain days, and your infertility doctor may have been trained (I was) to look at the cells and figure out what day in the cycle the cells were taken. How are we counting the days? Day 14 is the day of ovulation. It does not matter if ovulation occurred 9, 11, 14, 18 days from your last period, ovulation day we artificially call day 14 (many times ovulation is really day 14, but if it’s day 12, we change the 12 to 14.) and the next day is 15 etc.
The length of the follicular phase is usually not important when talking about luteal phase defects. This is the phase that gets shorter with age and increasing FSH levels. What probably happens is that the FSH rises, so the ovaries get stimulated earlier in the cycle and the follicular phase gets shorter. The length of the luteal phase is important. It should be around 14 days, and as short as 12 may be OK, longer is not an issue.
It’s the progesterone that makes these changes. Ovulation is around the start of progesterone production, and as the days of progesterone go on, the cells of the uterus make progressive changes.
So let’s say you are scheduled for a biopsy, and it’s day 25. You know it’s day 22 because you timed your ovulation using a kit or took your temperature or took hCG. You have your biopsy and the results come back saying your cells look like day 22 cells. There you have it, a luteal phase defect, because the development of your cells is more than 2 days behind. Next time we will go over why it’s not that simple and why biopsies are not done much anymore.
Dr. Licciardi
References:
  • van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2011 Oct 5 ;(10):CD009154.
  • Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA. Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertil Steril. 1999 Apr; 71(4):614-8.
  • Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2012 Nov 5. pii: S0015-0282(12)02238-8. doi: 10.1016/j.fertnstert.2012.09.019. [Epub ahead of print]
  • Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008 Mar; 89(3):554-61.

The Follicular Phase and the Luteal Phase

So you’ve been to the doctor and you were told you have some sort of defect, and you feel so happy that despite all you have been through some joker is now saying you’re defective: super.
Are you defective? Possibly, but probably not. Luteal Phase Defect, what does it mean? It has to do with the functioning of the menstrual cycle, so let’s go over that first.
The typical menstrual cycle, from the first day of bleeding to the next first day of bleeding, is divided into 2 parts. The first is from day 1 till ovulation. It’s called the follicular phase, because the most important thing is the growing follicle (the fluid filled cyst that holds the egg). If you are taking fertility drugs it’s the same, except that there may be more than one follicle developing at the same time. Here the main and most important hormone is estrogen, which comes from ovarian cells that surround the egg in the follicle (these are called granulosa cells). So estrogen does not come from the egg itself. The ovarian cells make more and more estrogen as the ovulation approaches. The most important job of the estrogen is to make the lining of the uterus thicker. Estrogen probably has little effect on the egg or embryo. That pretty much sums up the follicular phase. In a 28 day cycle it’s about 14 days, shorter in a shorter cycle, longer in a longer cycle. You will probably read about other hormones that may be involved in important ways during the follicular phase, but the estrogen is the key.
The second phase is the luteal phase. Here the key hormone is progesterone. Around the time of ovulation, the granulose cells that were making estrogen change and start making progesterone. The cyst that was the follicle stays a cyst but becomes the corpus luteum, the progesterone making machine. It’s called that because it luteum is Latin for yellow, and the cyst can be yellow in color. The most important role of progesterone is to cause changes in the endometrium so that the uterus can accept the embryo. Progesterone does not make the lining thicker, it just changes it. Without progesterone pregnancy can not occur. We know this because if the corpus luteum is removed in early pregnancy, the pregnancy will fail. Also, the abortion drug RU486 blocks progesterone and stops implantation.
Next time we will talk about more specifics of the luteal phase and “luteal phase defect”.
Dr. Licciardi

References:

  • Treloar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil 1967; 12:77.
  • Sherman BM, Korenman SG. Hormonal characteristics of the human menstrual cycle throughout reproductive life. J Clin Invest 1975; 55:699.
  • Messinis IE. Ovarian feedback, mechanism of action and possible clinical implications. Hum Reprod Update 2006; 12:557-71.
  • Hall JE, Schoenfeld DA, Martin KA, Crowley WF Jr. Hypothalamic gonadotropin-releasing hormone secretion and follicle-stimulating hormone dynamics during the luteal-follicular transition. J Clin Endocrinol Metab 1992; 74:600.